Common variants of genes encoding TLR4 and TLR4 pathway members TIRAP and IRAK1 are effective on MCP1, IL6, IL1β, and TNFα levels in type 2 diabetes and insulin resistance

Objective and design

Type 2 diabetes is a pandemic disease characterized by hyperglycemia, ineffective insulin use, and insulin resistance and affecting 1 in 11 people worldwide. Inflammation-related insulin resistance is thought to play an important role in the etiology of the disease. TLR4 is the central receptor of the natural immune system and has an important role as a trigger of the inflammatory response. The IRAK1 and TIRAP are members of the TLR4 pathway and involved in the TLR4-mediated inflammatory response. Genetic variants in the TLR4 gene or in the IRAK1 and TIRAP genes may have an important role in the development of insulin resistance and type 2 diabetes by disrupting the inflammatory response. In this direction, we aimed to investigate the relationship among TLR4 and IRAK1, TIRAP gene variants, and type 2 diabetes and insulin resistance, and investigate how these variants affect inflammatory factors (TNF-α, IL-6, MCP-1, and IL-1β).

Subjects and methods

In our study, a total of seven variations on the genes of TLR4 (rs4986790, rs4986791), IRAK1 (rs1059703, rs3027898, rs7061789), and TIRAP (rs8177374, rs8177400) were genotyped by the MassARRAY^® Iplex GOLD SNP genotyping in 100 type 2 diabetic patients and 100 non-diabetic individual. The TLR4 rs4986790 and rs4986791 variation was confirmed by PCR–RFLP method also. The serum IL1-β, IL6, MCP-1, and TNF-α levels were measured using enzyme-linked immunosorbent assay kits.

Results and conclusion

As a result of our study, no correlation was found among TLR4, IRAK1, and TIRAP gene variants and the risk of type 2 diabetes and insulin resistance. However, TNF-α, IL-6, MCP-1, and IL-1β levels were also associated with diabetes and insulin resistance (p?>?0.05). Although the gene variants were not significant in type 2 diabetes and insulin resistance groups, IRAK1, TLR4, and TIRAP gene variants were found to be associated with TNF-α, IL-6, MCP-1, and IL-1β levels.

     

Assessment of peripapillary retinal nerve fiber layer thickness in children with vitamin B12 deficiency

Purpose

Vitamin B₁₂ deficiency is a worldwide problem. It affects all ages, including children. It is one of the most common nutritional disorders and can cause harmful effects on the nervous system. In this study, we compared the peripapillary retinal nerve fiber layer thickness (RNFLT) in a healthy control group with children with vitamin B₁₂ deficiency. In our study, we aimed to evaluate the effect of vitamin B₁₂ deficiency on the RNFLT in children with the optical coherence tomography (OCT) method.

Methods

Sixty-six children with a diagnosis of vitamin B₁₂ deficiency (patient group) and 66 age- and sex-matched healthy children (control group) were enrolled in this prospectively designed study. Blood counts, vitamin B₁₂ levels, folate levels, and full biochemical parameters were obtained for all the subjects in each group. Peripapillary RNFLT measurements were performed with Cirrus HD spectral domain OCT.

Results

The thickness of the superior retinal nerve fiber layer (RNFL) in the vitamin B₁₂ deficiency group was significantly lower than that of the control group (p?=?0.037). Although the average thickness of the RNFL was lower in the patient group, there was no statistically significant differences (p?=?0.216). In the vitamin B₁₂ deficiency group, the average RNFL thickness and the superior RNFL thickness were significantly correlated with vitamin B₁₂ levels (r ₁?=?0.353, p ₁?<?0.004 and r ₂?=?0.416, p ₂?=?0.001, respectively).

Conclusion

Our study showed that a deficiency in vitamin B₁₂, elsewhere it is important for the development of the central nervous system, is associated with a reduction in the thickness of the superior RNFL.     

Distribution of gene mutations associated with familial normosmic idiopathic hypogonadotropic hypogonadism

Objective: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH. Methods: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH. Results: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency. Conclusions: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty.     

Visually evoked startle response in a patient with epilepsy: a case report and review of the literature

Both symptomatic and genetic, cases with hyperekplexia or startle seizures induced by acoustic stimuli, are previously reported. By contrast, startle response induced by visual stimuli is rare. While visual stimuli are more commonly associated with startle seizures, here we present an 11-year-old girl with epilepsy, motor-mental retardation, and spastic tetraparesis, who had repetitive startle responses by photic stimulation during the electroencephalogram recording, without any spike-and-wave discharges associated with the startles. We report this unique case with startle responses induced both by acoustic and photic stimuli and review the literature related to this exceptionally rare combination of symptoms.     

EEG abnormalities and long term seizure outcome in high functioning autism

Electroencephalographic abnormalities may occur in autistic spectrum disorders (ASD) even in the absence of clinical seizures. These abnormalities may vary from nonspecific changes to epileptiform abnormalities and are more common compared to the overall population. The level of intelligence is a significant risk factor for epilepsy in ASD. However, the relation between the functionality of the individuals with autism and the electroencephalographic (EEG) abnormalities, and the clinical significance of these abnormalities still remain relatively unclear. In this study we investigated the presence of EEG abnormalities in sixteen children diagnosed with high-functioning ASD. EEG recording was performed for at least 2 h and included at least 90 min of sleep activity. While none of the patients had clinical seizures, 5 patients (31.3%) were detected to have EEG abnormalities. Four of these were epileptiform (25%), and one patient developed seizure during follow-up. Our results support the fact that EEG abnormalities are observed at a higher rate also in ASD with a better functionality. The potential impact of EEG abnormalities on cognition and behavior, and the risk of epilepsy should be considered during long-term follow-up of these patients.     

Syrian Civil-War-Related Intraocular Foreign Body Injuries: A Four-Year Retrospective Analysis

Purpose: To analyze the data of patients who underwent vitreoretinal surgery due to intraocular foreign body (IOFB) injuries that occurred in the Syrian civil war. Methods: Seventy-eight eyes of 78 patients who underwent vitreoretinal surgery due to IOFB injuries that occurred during the Syrian civil war were analyzed. Results: Forty-four eyes (56.4%) had traumatic cataract, 44 (56.4%) had retinal tears, 42 (53.8%) had vitreous hemorrhage, 18 (23%) had retinal detachment, 12 (15.3%) had endophthalmitis, and eight eyes had hyphema (10.2%). IOFBs consisted of metal in 62 eyes (79.4%), stone in eight eyes (10.2%), organic material in four eyes (5.1%), and glass in four eyes (5.1%). Approximately 86% of the eyes had initial VAs of 4/200 or worse. However, VAs improved in 64 eyes (82%) after the surgeries. Conclusions: Despite delays in treatment and the severity of injuries, 82% (64/78) of the eyes had an improvement in VA after the surgeries.     

Prepubertal Unilateral Gynecomastia: Report of 2 Cases

Prepubertal unilateral gynecomastia is an extremely rare condition. At present, its etiology and management strategy are not well known. Two unrelated prepubertal boys of ages 8 and 9 who presented with complaints of unilateral enlargement of breast tissue are reported. Physical examination, biochemical, hormonal and oncologic work-up findings were normal. Both patients were treated with peripheral liposuction successfully. Histopathological and immunohistochemical examinations showed benign fibroglandular gynecomastia and intensive (3+) estrogen receptor expression in 100% of periductal epithelial cells. Although an extremely rare and generally benign condition, patients with prepubertal unilateral gynecomastia should have a full endocrine and oncologic work-up.